Dexmedetomidine enhances human lung fluid clearance through improving alveolar sodium transport

Abstract

Accumulating evidence shows that dexmedetomidine can attenuate lung edema with acute lung injury in experimental mouse and rat models, but the mechanisms of dexmedetomidine on human alveolar fluid transport are still unknown. We measured the effects of dexmedetomidine on alveolar fluid clearance in human lung lobes ex vivo. Moreover, we measured the regulation of transepithelial Na transport by dexmedetomidine in H441 cells by electrophysiological technique and Western blot method. Our results showed that intratracheal instillation of dexmedetomidine markedly increased the reabsorption of 5% bovine serum albumin instillate (19.8 ± 1.4%, P < 0.01 vs. Control, n = 5). Further studies suggested that dexmedetomidine increased amiloride-sensitive short-circuit currents in permeabilized H441 monolayers and whole cell amiloride-sensitive Na currents in a dose-dependent fashion. Real-time PCR and Western blot results showed that dexmedetomidine could enhance the mRNA and protein expression of α-ENaC subunit, while inhibiting the phosphorylation of ERK . These data demonstrate that dexmedetomidine could improve human lung fluid clearance and lung epithelial Na channel activity, and these effects may be mediated through the enhancement of α-ENaC expression and inhibition of ERK pathway.

Bone marrow mesenchymal stem cell‐conditioned medium facilitates fluid resolution via miR‐214‐activating epithelial sodium channels

“…H441 cells, an epithelial cell line from human distal lung, were acquired from the ATCC, and cultured as described previously. 23 , 33 For Ussing chamber assay, cells (∼5 × 10 6 cells/cm 2 ) were grown on Costar Transwells (Corning‐Costar, Lowell, MA, USA) for 24 hours until reaching confluence. Then, cells were cultured in air‐liquid interface model, and the basolateral compartment medium was replaced every 48 hours.…”

Role of biomarkers and molecular signaling pathways in acute lung injury

“…These findings suggest that BMSC‐exo, with their contained miR‐199a‐3p, could serve as a novel pharmacological intervention for the treatment of ALI [8]. In another study, dexmedetomidine increased lung epithelial Na + channel activity and human lung fluid clearance; these effects could be mediated by enhancing α‐ENaC expression and inhibiting the ERK1/2 pathway [9].…”

Geriatric Anesthesia-related Morbidity and Mortality in China

“…[ 19 ] The pain associated with thoracic surgery may release the inflammatory factors that might suppress the pulmonary function. [ 20 ] Thus, both laboratory and clinical studies suggested that dexmedetomidine may exert a protective effect on the pulmonary system,[ 21 22 ] leading to a reduced incidence of respiratory complications. The ischemic preconditioning combined with dexmedetomidine might decrease the incidence of postoperative pulmonary complications by alleviating the inflammatory response and oxidation reaction, which are corroborated by the prevention of the surge of interleukin-6 (IL-6) and enhancement of the activation of superoxide dismutase.…”